Atraumatic stent and method and apparatus for making the same

ABSTRACT

A method of braiding a stent includes braiding a number of elongate filaments around a mandrel using tensioned braiding carriers without spooling the filaments to the tensioned braiding carriers to form a braided stent having atraumatic ends.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/204,508, filed Jul. 7, 2016, issued as U.S. Pat. No. 10,278,842;which is a continuation of U.S. application Ser. No. 14/096,307, filedDec. 4, 2013, issued as U.S. Pat. No. 9,388,517; which is a continuationof U.S. application Ser. No. 13/912,445, filed Jun. 7, 2013, issued asU.S. Pat. No. 8,677,874; which is a continuation of U.S. applicationSer. No. 13/441,649, filed Apr. 6, 2012, issued as U.S. Pat. No.8,459,164; which is a continuation of U.S. application Ser. No.12/630,068, filed on Dec. 3, 2009, issued as U.S. Pat. No. 8,151,682;which claims priority to U.S. Provisional Application No. 61/147,307,filed Jan. 26, 2009; the content of each incorporated herein byreference.

FIELD OF THE INVENTION

The present invention is related to an atraumatic stent and methods,apparatus and systems for making the same. More particularly, thepresent invention is related to an atraumatic braided stent and braidingmethods, braiding mandrels and braiding machines for making the same.

BACKGROUND OF THE INVENTION

Braided stents have typically been braided on a smooth mandrel. The endsof the braiding wires were typically gathered beyond an end of abraiding mandrel, and the wires where then secured, typically by tyingor taping, to the mandrel end portion, after which braiding, either byhand or machine, commenced.

The braiding angle was controlled by the angle at which the stent wireswere disposed over the mandrel. Many stents, however, use metallic wireswhich may shift or move during braiding as a result of forces impartedon the wires during the braiding. This may result in a variation of thebraiding angle though the stent, in particular for stents braided withvaried diameters, such as flared, flanged and/or tapered stents.Variation in the braiding angle may result in undesirable variation ofradial expansion or compression forces or deployment forces of the soformed stent. Such variations may also effect the consistency of thesize of the openings, e.g., cell size, across the stent.

Wire used in the fabrication of the stent is generally fed from a spoolonto the mandrel. In this manner, multiple stents could be formed byfeeding enough material to the mandrel during the braiding process andthereafter cutting the resulting long stent into multiple smallerstents. After braiding the long stent, the wire portions gathered beyondthe mandrel end were trimmed. The trimming of such excess wireneedlessly wastes material. As many early stents were braided simplywith stainless steel wires, the cost of discarding this excess wirematerial was minimal. More recently, however, stent wires of moreexpensive materials, such as nitinol or composite nitinol have beenused. The cost of the discarded material has become much more costly.

Thus, there is a need in the art to provide a method for braiding astent where material costs are minimized and where variations in thestent configuration, including braiding angle, are also minimized.Further, there is a need in the art to provide a method for braiding astent with atraumatic ends from discrete wire lengths so that thebraiding angle(s) of the stent and the size and orientation of theatraumatic ends are controllably provided to produce atraumatic stentswith consistency while allowing for mass production of the atraumaticstents. Moreover, there is a need optimize stent manufacturing to moretightly control stent specifications, including optimizing materialcontrol and including ability to create any specific quantity of customstents as desired.

SUMMARY OF THE INVENTION

The present invention provides braiding methods, braiding mandrels,braiding machines and braided stents which avoid and solve theundesirable concerns of the prior art. The braided stents of the presentinvention have a substantially controlled braiding angle, including asubstantially constant braiding angle, if desired, throughout itslongitudinal expanse, including portions having varied diameters, suchas tapered portions, flared portions and/or flanged portions. Forexample, a substantially constant braiding angle, for example but notlimited to 110°, may be desired throughout the longitudinal expanse of astent, including portions having varied diameters. Additionally, thebraided stents of the present invention may have varied diameterportions where the braiding angle is controllably different in onevaried diameter portion as compared to another varied diameter portionand/or is controllably different in one or more varied diameter portionsas compared to the longitudinal expanse of the stent. Further, thecontrolled braiding angle of the inventive stent may vary from oneangle, for example but not limited to 90°, at one end, to a differentangle, for example but not limited to 120°, at an opposed second endwhere not only the end angles but also all of the transition anglesbetween the opposed ends are controlled. Such inventive stents areproduced by methods and devices of the present invention which include,inter alia, braiding mandrels having specifically designed grooves andprojections and constant force braiding carriers for tangentiallydelivering stent filaments for braiding the filaments onto suchspecifically designed mandrels.

In one embodiment of the present invention, a method of braiding a stentis provided. The method may include the steps of (a) providing a numberof elongate filaments, each of the filaments having opposed ends and anintermediate portion between the opposed ends; (b) providing a number oftensioned braiding carriers; (c) providing a braiding mandrel havingopposed proximal and distal ends, the braiding mandrel comprising anumber of circumferentially spaced-apart securement projections at thedistal end of the braiding mandrel; (d) securably disposing theintermediate portion of one of the filaments to one of the securementprojections; (e) securing one of the opposed ends of the one filament toone of the tensioned braiding carriers without spooling the one filamentto the one constant force braiding carrier; (f) securing the otheropposed end of the one filament to a different second tensioned braidingcarrier without spooling the one filament to the second tensionedbraiding carrier; (g) repeating steps (d) through (f) until all of theintermediate portions of the filaments are securably disposed todifferent ones of the securement projections and until each end of thenumber of filaments are secured to a different one of the tensionedbraiding carriers; (h) moving the constant force carriers around themandrel, for example in a generally circular and serpentine motion; and(i) longitudinally advancing the mandrel in a direction substantiallyperpendicular to the motion of the constant force carriers to braid thefilaments to form a braided stent. Advancing the mandrel may includemoving the mandrel with respect to the perpendicular motion of thetensioned braiding carriers, moving the tensioned braiding carrierslongitudinally with respect to the mandrel, and combinations thereof.The tensioned braiding carriers each may include a retractable carrierfilament for releasably securing a stent filament thereto. The tensionedbraiding carriers each may also include a wheel around which theretractable carrier filament may be coiled.

In another embodiment of the present invention, a method for braiding astent comprises the steps of (a) providing a number of elongatefilaments, each of the filaments having opposed ends and an intermediateportion between the opposed ends; (b) providing a number of braidingcarriers; (c) providing a braiding mandrel having opposed proximal anddistal ends, the braiding mandrel comprising a number ofcircumferentially spaced-apart securement projections at the distal end,the mandrel further comprising a plurality of grooves; (d) securablydisposing the intermediate portion of one of the filaments to one of thesecurement projections at the distal end of the mandrel; (e) securingone of the opposed ends of the one filament to one of the braidingcarriers; (f) securing the other opposed end of the one filament to adifferent second braiding carrier; (g) repeating steps (d) through (f)until all of the intermediate portions of the filaments are securablydisposed to different ones of the securement projections and until eachend of the number of filaments are secured to a different one of thebraiding carriers; (h) moving the braiding carriers around the mandrel,for example in a generally circular and serpentine motion; (i)longitudinally advancing the mandrel relative to a directionsubstantially perpendicular to the motion of the braiding carriers tobraid the filaments to form a braided stent; and (j) applying a constanttension force from the braiding barriers to the filaments during thebraiding steps (h) through (i).

In yet another embodiment of the present invention, a method forbraiding a stent comprises the steps of (a) providing a number ofelongate filaments, each of the filaments having opposed ends and anintermediate portion between the opposed ends; (b) providing a number oftensioned braiding carriers; (c) providing a braiding mandrel havingopposed proximal and distal ends, the braiding mandrel comprising anumber of circumferentially spaced-apart securement projections at thedistal end, the braiding mandrel further comprising a plurality ofgrooves; (d) securably disposing the intermediate portion of one of thefilaments to one of the securement projections at the distal end of thebraiding mandrel; (e) securing one of the opposed ends of the onefilament to one of the tensioned braiding carriers without spooling theone filament to the one tensioned braiding carrier; (f) securing theother opposed end of the one filament to a different second tensionedcarrier without spooling the one filament to the second tensionedcarrier; (g) repeating steps (d) through (f) until all of theintermediate portions of the filaments are securably disposed todifferent ones of the securement projections and until each end of thenumber of filaments are secured to a different one of the tensionedcarriers; (h) moving the tensioned carriers around the mandrel, forexample in a generally circular and serpentine motion; and (i)longitudinally advancing the mandrel relative to a directionsubstantially perpendicular to the motion of the tensioned carriers tobraid the filaments by tangentially disposing the filaments into thegrooves to braid the filaments to form a braided stent.

In a still further embodiment of the present invention, a braided stentis provided. The braided stent comprises a plurality of elongatefilaments inter-braided to form a tubular well structure, the filamentsbeing inter-braided at a braiding angle formed at crossing filamentlocations; the tubular wall structure comprising a first portion havinga first diameter, a second portion having a second diameter which isdifferent from the second diameter and a transition portion disposedbetween the first portion and the second portion; wherein the braidingangles in the first portion, the second portion and the transitionportion are substantially equal. Alternatively, the braiding angles ofthese portions may be different, but nevertheless controlled. Moreover,the stents of the present invention are not limited to those having avaried diameter and/or flared or flanged portions. A constant diameteror substantially constant diameter may also be provided. Such a constantor substantially constant diameter stent may have improved tolerances,i.e., fewer variations, of cell configuration, for example braidingangles, cell size and the like.

Further, a braiding mandrel for braiding the tubular stent of thepresent invention desirably comprises an elongate tubular member havingopposed proximal and distal ends; securement projectionscircumferentially disposed at spaced-apart locations at the distal endfor engaging a filament from a braiding machine; a plurality of annularor annular disposed grooves along the longitudinal length of the member.The grooves may extend at an angle from about 5° to about 85° from alongitudinal axis of the member.

Use of the optimized braiding techniques and braiding components of thepresent invention allow a manufacturer to make a customized stent. Sucha customized stent may be specific to any one set of specifications,including but not limited to braiding angle, stent diameter, stentlength, stent shape and then like. Moreover, such customized stents maybe produced with optimized manufacturing techniques, thereby providingcustomized stents with improved quality control as compared to the priorart.

These and other features and advantages of the present invention willbecome apparent from the following detailed description of illustrativeembodiments thereof, which is to be read in connection with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side elevational schematic view of braiding machine of thepresent invention.

FIG. 2 is a front view of the braiding machine of FIG. 1 taken along the2-2 axis.

FIG. 3 is an alternate embodiment of the braiding machine of FIG. 2.

FIG. 4A depicts a stent according to the present invention.

FIG. 4B is an exploded view of the stent of FIG. 4A illustrating aone-under and one-over braiding configuration.

FIG. 4C is an exploded view of the stent of FIG. 4A illustrating atwo-under and two-over braiding configuration.

FIG. 4D is an exploded view of the stent of FIG. 4A illustrating a pairof filaments in a one-under and one-over braiding configuration.

FIG. 5 is a side elevational view of the braiding mandrel of the presentinvention.

FIG. 6 depicts a braiding mandrel having a substantially constantdiameter according to the present invention.

FIG. 7 is an exploded view of a portion of the mandrel of FIG. 5depicting the raised mandrel projections.

FIGS. 8-10 depict details of the raised mandrel projections of FIG. 7.

FIG. 11 is an exploded view of a portion of the distal end of thebraiding mandrel of FIG. 5 or 6 depicting raised projection on thedistal end.

FIG. 12 is a top view of a raised projection of FIG. 11.

FIG. 13 depicts the braiding mandrel having middle portions of the stentfilaments secured to the raised projections.

FIG. 14 depicts stent filaments being braided over the mandrel of thepresent invention.

FIG. 15 is an exploded view of the proximal end of the braiding mandrelof the present invention.

FIGS. 16A and 16B are partial exploded views of a transitional portionof the braiding mandrel of the present invention.

FIG. 17 depicts a braiding mandrel of the present which is free of theraised projections.

FIGS. 18-21 illustrate alternate embodiments for securing stentfilaments at the distal end of the braiding mandrel.

FIG. 22 is a schematic depiction of a constant force carrier of thepresent invention.

FIG. 23 is a schematic of a clip mentioned in FIG. 1.

FIG. 24 is a schematic of an alternate embodiment of a constant forcebobbin carrier of the present invention.

FIG. 25 is a schematic of a method of forming the stent of the presentinvention.

FIG. 26 is a schematic of another method of forming the stent of thepresent invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 is a side elevational schematic view of braiding machine 10 ofthe present invention. Certain features of the braiding machine 10, suchas motors, controls, safety features, etc., are not shown forsimplicity. The braiding machine 10 of the present invention, however,may suitably include such features without limitation. Braiding machine10 includes a number of notch gears 12. Each notch gear 12 may include aone or more, typically a pair of, tensioned or constant force braidingcarriers 14 disposed thereon. The tensioned or constant force braidingcarriers 14 have a retractable carrier filament 16. The retractablecarrier filament 16 is releasably secured to a stent-forming filament 20via a clip 18. The stent-forming filaments 20 are braided over a mandrel22 to form a stent 24 of the present invention.

The stent-forming filaments 20 are braided typically in a one-over andone-under pattern to form a braided tubular structure, i.e., stent 24.Other braiding arrangements are possible, including but not limited tothose depicted in FIGS. 4C and 4D. The braiding operation isschematically depicted in FIG. 2, which is a front view of the braidingmachine 10 of FIG. 1 taken along the 2-2 axis. Note that as used hereinthe term braiding includes weaving and the like. FIG. 2 depicts thebraiding machine 10 as having twenty notch gears 12 arranged in agenerally circular configuration 26. The number of notch gears 12 usedwith the braiding machine 10 is not limited to twenty and any suitablenumber of notch gears 12 may be used. Each notch gear 12 is adapted torotate in the opposite direction as its neighboring notch gear 12, asillustrated by arrows A and B in FIG. 2. This counter-rotation movementof the notch gears 12 passes the braiding carriers 14 in a sinusoidalfashion from one notch gear 12 to an adjacent or juxtaposed notch gear12, thus causing the carriers 14 to revolve, or move in acircumferential manner, about a longitudinal axis L on which the circleof notch gears 12 is desirably centered. The circular configuration 26of the notch gears 12 and carriers 14 achieve a generally circular butsinusoidal movement of the carriers 14 to braid the filaments 20 overthe mandrel 22 in a one-over and one-under fashion to form the stent 24.

As depicted in FIG. 3, not every carrier 14 need have a filament 16, 20disposed there with. For example, carriers 14′ may not have a filament16, 20 while carriers 14 may have the filaments 16, 20. In such amanner, the number of filaments 20 making the stent 24 may be alteredwhile using the same braiding machine 10.

During braiding, the mandrel 22, around which braided stent 24 isformed, is moved in a controlled manner substantially along alongitudinal axis L about which the circle 26 of notch gears 12 iscentered and about which the carriers 14 revolve. FIG. 1 illustrates,from the side, such a configuration. During braiding, filaments 20extend from the braiding machine 10 to the mandrel 22 in a generallyconical configuration, as shown in FIG. 1. The present invention,however, is not so limited. For example, as an alternative or inaddition to, the mandrel may stay fixed in place and the braiding orweaving machine may be moved the length of the mandrel.

As illustrated in FIG. 2, as two carriers 14 cross one another alongtheir generally circular but sinusoidal movement, their respectivefilaments 20 form an overlap such that the filament 20 associated with acarrier 14 on the outer radius 28 of the circle 26 of the notch gears 12is disposed radially outward (with respect to the axis of the stentbeing assembled) relative to the filament 20 associated with a carrier14 on the inner radius 30 of the circle 26 of notch gears 12. Thecarriers 14 depicted toward the outer radius 28 of the circle 26 ofnotch gears 12 move in a generally counterclockwise direction, and thecarriers 14 disposed toward the inner radius 30 of the circle 26 ofnotch gears 12 move in a generally clockwise direction.

The space contained within the cone formed by the filaments 16, 18extending between the carriers 14 and the mandrel 22 and including thespace occupied by the mandrel 22 is referred to herein as the “braidingzone” 32, as depicted in FIG. 1. Although the angles α₁ and α₂ of thefilament 16, 20 to the mandrel 22 may be varied as desired, α₁ and α₂preferably each comprise an angle of approximately 55° when the braidingangle of a braided stent β is approximately 110°. These angles may varydependent upon, inter alia, the exact radial position of the carriers 14relative to the mandrel 22. Further, these angles are nonlimiting andany suitable braiding angle β, including acute or obtuse braiding angleβ. For example, the braiding angle β may vary from about 10° to about170°, desirably from about 30° to about 150°, preferably from about 100°to about 120°. As used herein, the phrase “substantially along thelongitudinal axis” as used with respect to the alignment of the movingmandrel means that the mandrel does not have to be perfectly centered inthe braiding zone, but merely needs to be aligned close enough to thelongitudinal axis L such that the angles of the filaments between themandrel and the carriers allows the braiding operation to create afunctional braid without tangling the filaments.

FIG. 4A depicts a stent 24 according to the present invention. The stent24 may include a first atraumatic end 34 and an opposed secondatraumatic end 38. The first atraumatic end may be formed by bending thefilaments 20 at or about the middle portion of the length of thefilaments 20 to form bends 36 thereat. The second opposed atraumatic end38 may be formed by bending the filaments 20 into closed loops 39. Thefilaments 20 forming the closed loops 39 may be secured to one and theother by welds 41. The stent 24 of the present invention is not limitedto the use of welds 41 to join stent filaments 20, and other mechanicalmeans, such as the use of hypotubes, twisting or tying of the filamentsand the like, may suitably be used. The stent 24 of the presentinvention may also include one or more outwardly flared or flangedportions 40. In such a case, the diameter of the flared portion 40 isgreater than the diameter of the longitudinal expanse portion 42 of thestent 24. The longitudinal expanse portion 42 of the stent 24 may be aconstant diameter, including a substantially constant diameter. Suchstent configurations are non-limiting, and other stent configurationsmay be achieved with the systems, devices and methods of the presentinvention. For example, the stent 24 may include outwardly flaredportions at both ends 34, 38, may have a tapered configuration in placeof or in conjunction with the longitudinal expanse portion 42 of thestent 24.

Further, the braiding angle β throughout the stent 24, including theflanged portion 40 and the longitudinal expanse portion 42, issubstantially constant. For example, as depicted in FIG. 4A, thebraiding angle β is about 110°±3°, desirably about 110°±1°. Stents ofthe prior art typically have a variation of ±10° or greater in stenttransitional regions, such as the flared or flanged portions of theirstents. Such variations, however, present undesirable variability instent performance, such as radial expansion force, radial compressionforce or deployment force. The present invention avoids such undesirablevariations through the use of, inter alia, the tensioned or constantforce braiding carriers 14 (described in further detail below inconjunction with the description of FIG. 22), the constant force bobbincarriers 110 (described in further detail below in conjunction with thedescription of FIG. 24), the braiding mandrel 22 having raisedprojections 52, 56, (optionally) 70 (described in further detail belowin conjunction with the description of FIGS. 5-16B), and/orstent-filament-holding securement projections 48 on the mandrel 22(described in further detail below in conjunction with the descriptionof FIGS. 6, 14 and 15).

The one-under and one-over braiding configuration of the stent 24 ofFIG. 4A is depicted in an exploded view in FIG. 4B. As depicted in FIG.4B, the filaments 20 alternate in a braiding pattern having a 1/1intersection, i.e., one-under and one-over pattern. The stent 24,however, is not so limited. As depicted in FIG. 4C, stent 24 may includethe filaments 20 braided in a two-under and a two-over pattern. Otherbraiding patterns known in the art may also be suitably be used.Further, as illustrated in FIG. 4D, stent 24 may be braided by using apair of filaments 20′ in a one-under and one-over pattern. The filaments20′ may be the same or may be different, i.e., may have the same ordifferent dimensions, shapes and/or materials of construction. Moreover,the filaments 20′ may suitably be braided in other braided patterns,such as but not limited to, for example, the two-under and two-overpattern. Desirably, the braided filaments 20, 20′ non-interlockinglyengage one and the other in the braided pattern. Such non-interlockingbraiding pattern excludes, if desired, inter-twisting, inter-looping,inter-engaging and the like at the intersection of the braided filaments20, 20′. If desired, the braided or woven filaments 20, 20′ may bebraided or woven in an interlocking manner.

Desirably, the filaments 20 are made from any suitable implantablematerial, including without limitation nitinol, stainless steel,cobalt-based alloy such as Elgiloy®, platinum, gold, titanium, tantalum,niobium, polymeric materials and combinations thereof. Useful polymericmaterials may include, for example, polyesters, including polyethyleneterephthalate (PET) polyesters, polypropylenes, polyethylenes,polyurethanes, polyolefins, polyvinyls, polymethylacetates, polyamides,naphthalane dicarboxylene derivatives, natural silk, polyvinyl chloride,polytetrafluoroethylene, including expanded polytetrafluoroethylene(ePTFE), fluorinated ethylene propylene copolymer, polyvinyl acetate,polystyrene, poly(ethylene terephthalate), naphthalene dicarboxylatederivatives, such as polyethylene naphthalate, polybutylene naphthalate,polytrimethylene naphthalate and trimethylenediol naphthalate,polyurethane, polyurea, silicone rubbers, polyamides, polycarbonates,polyaldehydes, natural rubbers, polyester copolymers, styrene-butadienecopolymers, polyethers, such as fully or partially halogenatedpolyethers, and copolymers and combinations thereof. Further, useful andnonlimiting examples of polymeric stent materials includepoly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), poly(glycolide) (PGA),poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-co-glycolide)(PLLA/PGA), poly(D,L-lactide-co-glycolide) (PLA/PGA),poly(glycolide-co-trimethylene carbonate) (PGA/PTMC), polydioxanone(PDS), Polycaprolactone (PCL), polyhydroxybutyrate (PHBT),poly(phosphazene) poly(D,L-lactide-co-caprolactone) PLA/PCL),poly(glycolide-co-caprolactone) (PGA/PCL), poly(phosphate ester) and thelike. Wires made from polymeric materials may also include radiopaquematerials, such as metallic-based powders, particulates or pastes whichmay be incorporated into the polymeric material. For example theradiopaque material may be blended with the polymer composition fromwhich the polymeric wire is formed, and subsequently fashioned into thestent as described herein. Alternatively, the radiopaque material may beapplied to the surface of the metal or polymer stent. In eitherembodiment, various radiopaque materials and their salts and derivativesmay be used including, without limitation, bismuth, barium and its saltssuch as barium sulphate, tantulaum, tungsten, gold, platinum andtitanium, to name a few. Additional useful radiopaque materials may befound in U.S. Pat. No. 6,626,936, which is herein incorporated in itsentirely by reference. Metallic complexes useful as radiopaque materialsare also contemplated. The stent may be selectively made radiopaque atdesired areas along the wire or made be fully radiopaque, depending onthe desired end-product and application. Further, the filaments 20 havean inner core of tantalum, gold, platinum, iridium or combination ofthereof and an outer member or layer of nitinol to provide a compositewire for improved radiocapicity or visibility. Desirably, the inner coreis platinum and the outer layer is nitinol. More desirably, the innercore of platinum represents about at least 10% of the wire based on theoverall cross-sectional percentage. Moreover, nitinol that has not beentreated for shape memory such as by heating, shaping and cooling thenitinol at its martensitic and austenitic phases, is also useful as theouter layer. Further details of such composite wires may be found inU.S. Patent Application Publication 2002/0035396 A1, the contents ofwhich is incorporated herein by reference. Preferably, the filaments 20are made from nitinol, or a composite wire having a central core ofplatinum and an outer layer of nitinol.

FIG. 5 is a side elevational view of a braiding mandrel 22 according tothe present invention. The braiding mandrel 22 is a tubular, typicallymetal such as stainless steel, cylindrical member having a distal end 44(distal from the circle 26 of notch gears 12 when disposed on thebraiding machine 10) and an opposed proximal end 46 (proximal to thecircle 26 of notch gears 12 when disposed on the braiding machine 10).The distal end 44 includes securement projections 48, which, asdescribed below, are useful for engaging the stent filaments 20 prior tothe commencement of braiding. The distal end 44 further includes adistal portion 50 which has a larger diameter than the longitudinalportion 54 of the mandrel 22. After braiding the filaments 20, thedistal mandrel portion 50 forms the flared stent portion 40, and thelongitudinal mandrel portion 54 forms the longitudinal expanse stentportion 42. Both the distal mandrel portion 50 and the longitudinalmandrel portion 54 may include raised mandrel projections 52 and 56,respectively. As described below, the raised mandrel projections 52, 56are useful for forming guides for receiving the filaments 20 duringbraiding. The larger diameter portion may include a flared portion, astepped portion and the like. Further, the larger diameter portion maybe disposed anywhere along the length of the mandrel 22. Moreover, themandrel 22 may have multiple larger diameter portions, which may be thesame or different.

The present invention, however, is not limited to the used of a dualsized or flared mandrel 22. For example, as depicted in FIG. 6, braidingmandrel 22′ may be a substantially constant diameter mandrel, which isuseful for braiding substantially constant diameter stents 24. Thedepicted shapes of the mandrels 22, 22′ are non-limiting and othershaped mandrels may suitably be used, such as dual flared or flangedmandrel, tapered mandrels, and the like. Moreover, the raised mandrelprojections 52, 56 need not be present along the whole braiding lengthand/or circumference of the braiding mandrel 22. Selected portion of thebraiding mandrel 22 may be free or partially free of the raised mandrelprojections 52, 56 depending on the characteristics of the stent 24 tobe produced.

FIG. 7 is an exploded view of a portion of the mandrel 22 furtherdepicting the raised mandrel projections 52, 56. The raised mandrelprojections 52, 56 are arranged in a regular pattern over the mandrel 22so that adjacent or juxtaposed raised mandrel projections 52, 56 formguides or channels 58 for receiving the stent filaments 20 duringbraiding. FIGS. 8-10 further detail the raised mandrel projections 52,56 of the present invention. As depicted in FIG. 8 the raised mandrelprojections 52, 56 are in the shape of a square or rectangular pyramid,having a square or rectangular base 60 and four triangular sides 62. Asdepicted in FIG. 9, the raised mandrel projections 52, 56 may have atruncated top portion 64. The top portion 64 may be somewhat rounded(not shown), if desired. Truncated and/or rounded top portions 64 areuseful for easy removal of the stent 24 from the mandrel 22. Forexample, to remove the stent 24 from the mandrel 22 the stent 24 may belongitudinally compressed which causes the diameter of the stent 24 toincrease. The stent filaments 20 may then clear over the truncatedand/or rounded top portions 64, thereby releasing the stent 24 from themandrel 22. Depending upon, for example, the braiding angle of the stentfilaments 20 and/or the height of the raised mandrel projections 52, 56,the raised mandrel projections 52, 56 may be truncated to so form thetruncated and/or rounded top portions 64 of the mandrel 22. Truncatedand/or rounded top portions 64 may also be useful for guiding the stentfilaments 20 into the guides or channels 58 of the mandrel 22. Further,as depicted in FIG. 10, the raised mandrel projections 52, 56 mayfurther include a square or rectangular base portion 66 to furtherdefine the guides or channels 58 of the mandrel 22. Such features of theraised mandrel projections 52, 56 are useful for forming mandrel guidesor channels 58 so that accurate placement of the stent filaments 20 isachieved during braiding, including accurate placement of the stentfilaments 20 over dimensional variations of the mandrel 22, such asflared or tapered portions. The present invention, however, is notlimited to the use square or rectangular pyramid shaped raised mandrelprojections 52, 56, and other suitably shaped projection may suitably beused. For example, pins or projections, including removable pins orprojections may suitably be used. The raised mandrel projections 52, 56may be formed by cutting or etching away portion of the mandrel, such asby laser cutting, machine cutting, chemical etching, and the like.Further, the guides or channels 58 may be formed as grooves in themandrel. Moreover, the raised mandrel projections 52, 56 forming thechannels 58 may be on a collar or sleeve which may be releasably securedto the braiding mandrel itself.

FIG. 11 is an exploded view of a portion of the distal end 44 of thebraiding mandrel 22. The securement projections 48 are depicted as beingraised tabs 48′. The raised tabs 48′ have a rounded face 49 for ease ofsecurement of the stent filaments 20 and for safety by generallyeliminating shape and pointed faces on the mandrel 22. As depicted inFIG. 12, the raised tab 48′ is useful for bending a stent filament 22about an under portion 51 of the raised tab 48′. The under portion 51 ofthe raised tab 48′ is recessed from the rounded face 49 to secure thestent filament wire 20 thereat. Further, the under portion 51 of theraised tab 48′ may be contoured so that the shape of the bend 36 of atthe distal end 34 of the stent 24 corresponds to the shape of the underportion 51 of the raised tab 48′. The present invention, however, is notlimited to such described under portion 51 of the raised tab 48′ assecurement projections 48, and as described below other configurationsfor the securement projections 48 may suitably be used. Moreover, thepresent invention is not limited to the securement of one stent filament20 around one raised tab 48′. For example, if desired, two or more stentfilaments 20, which may be the same or different including differentmaterial and/or specifications, may be secured about one raised tab 48′and then braided according to the techniques of the present invention.

FIG. 13 depicts the braiding mandrel 22 having middle portions of thestent filaments 20 secured to the raised projections 48′. Further, thestent filaments 20 are disposed within the channels 58 of the mandrel 22formed between juxtaposed raised projections 52, 56. FIG. 14 depicts thestent filaments 20 being braided over the mandrel 22. Further, one end,for example the proximal end 46, of braiding mandrel 22 may bereleasably secured to the mandrel 22′ of the braiding machine 10 by asleeve 47. Other arrangements may be suitably be used to secure thebraiding mandrel 22 to the mandrel 22′ of the braiding machine 10.

FIG. 15 is an exploded view of the proximal end 46 of the braidingmandrel 22. The proximal end of the braiding mandrel 22 may includeprojections 45 which are useful for forming the closed loops 39 of stent24. Such closed loops may be formed by bending the filaments 20 aroundthe projections 45 (not shown). Details for forming such closed loops 39may be found in U.S. Patent Application Publication Nos. 2005/0049682 A1to Leanna et al.; 2005/0256563 A1 to Clerc et al.; and 2006/0116752 A1to Norton et al., the contents of which are incorporated herein byreference.

The braiding mandrels 22 of FIGS. 5-15 are depicted as being useful formanufacturing a single stent. The braiding mandrels 22 of the presentinvention, however, are not so limited. For example, several stents 24may be produced on a single mandrel 22 by providing different mandrelregions each having the securement projections 48 for commencing thebraiding of a stent portion; channels 58 for receiving and controllingthe stent filaments 20 within the particular section; and projections 45for finishing the atraumatic stents 24 of the present invention. Theseveral or multiple stents 24, i.e., two or more, may be the same or mayhave different stent configurations including stent diameters and stentlengths. In other words, the techniques and devices of the presentinvention allow for the manufacture of a highly customizable stent orhighly customizable stents. Such customizable aspects of the stent mayinclude but are not limited to the customization of stent lengths, stentdiameters, stent curvatures, stent geometries, including atraumaticstent end geometries, and the like.

FIGS. 16A and 16B are partial exploded views of a portion of thebraiding mandrel 22 of the present invention. As depicted in FIG. 16A,the distal mandrel portion 50 has a larger diameter than a diameter ofthe longitudinal mandrel portion 54. The transition 53 between thedistal mandrel portion 50 and the longitudinal mandrel portion 54 is asimple step down in mandrel 22 diameters. As depicted in FIG. 16B, atransition region 68 is disposed between the larger distal portion 50and the smaller the longitudinal mandrel portion 54. The transitionregion 68 is a sloped, desirably conical, region between the twodiameters. The transition region 68 may further include raised mandrelprojections 70, similar to the above-described shaped raised projections52, 56.

While aspects of the present invention have been described as using amandrel 22, 22′ having raised projections 52, 56 to provide, the presentinvention is not so limited. For example, as depicted in FIG. 17, whereit is desirable, a braiding mandrel 22″ which is free or substantiallyfree of the above described raised projections 52, 56 may suitably beused. Such a mandrel 22″ may still include the above describedsecurement projections 48 at its distal end 44 and projections 45 (notshown) at its proximal end 46.

FIGS. 18-21 illustrate alternate embodiments of the securementprojections 48 for securing stent filaments 20 at the distal end 44 ofthe braiding mandrel 22. These embodiments may be releasably secured tothe distal end 44 of the braiding mandrel 22 or in some cases integrallyformed with the distal end 44 of the braiding mandrel 22, such as butnot limited to the above described raised tabs 48′. FIGS. 18-19 depict awagon wheel arrangement 72 for securing stent filaments 20 at the distalend 44 of the braiding mandrel 22. The wagon wheel 72 may include pins74 around which the stent filaments 20 may be disposed. The stentfilaments 20 may be disposed about the inner portions 76 of the pins 74,but if desired the stent filaments 20 may be disposed outer pin portion77. The wagon wheel 72 may further include an undulating surface 78. Theundulating surface 78 is useful in positioning the stent filaments 20within the wagon wheel 72. Further, the shape of the undulating surface78 may be altered to conform to the desired angle of the bends 36 of thestent 24.

FIG. 20 depicts a mandrel 22″ having holes 80 at its distal end. Screws,pins, tabs, detents and the like (not shown) may be inserted into theholes 80 for securing stent filaments 20 (not shown) thereat. Asdepicted in FIG. 21, a cap 82 may be used in conjunction with theembodiment of FIG. 20. The cap 82 may have a plurality of semicircularnotches 84 which receive the pins or screws described in conjunctionwith FIG. 20. The cap 82 may further include projections 86 with angularor sloped surfaces 85 which are useful for setting and orientation,configuration and/or angle of the bends 36 of the stent 24. While thisembodiment of the projections for securing the stent filaments 20 isshown as being integrally formed into the mandrel 22″, the holes 80 maybe integrally formed in any of the other described mandrels 22, 22′, ormay be formed as a separate device which may be releasably secured toany of the braiding mandrels 22, 22′, 22″.

FIG. 22 is a schematic depiction of a tensioned or constant forcebraiding carrier 14 of the present invention. The constant force carrier14 may include a frame 88 for holding wheels 90, 92, 94, 96 and spring98. The retractable carrier filament 16 may have one end securably woundaround wheel 92. The retractable carrier filament 16 may exit theconstant force carrier 14 via wheels 94, 96, as shown. The wheels 94, 96are useful in guiding the retractable carrier filament 16 toward thebraiding zone 32. Spring 98 generally imparts a constant force fromwheel 90 to wheel 92 to provide, in part, a constant tension to theretractable carrier filament 16. The retractable carrier filament 16 mayitself coil or wrap around wheel 92 to be in communication with thetension applied by the spring 98. Further, as the stent 24 is beingbraided, the retractable carrier filament 16 may uncoil or unwrap fromthe wheel 92 to accommodate the movement of the stent filaments 20within the braiding zone 32. The bottom portion 89 of the frame 88 ofconstant force carrier 14 may be releasably secured to the notch gear 14as schematically depicted in FIGS. 1-2. The constant force carrier 14 ofFIG. 22 does not include a bobbin having stent forming filaments 20wound thereon. In other words the constant force carrier 14 of FIG. 22includes the retractable carrier filament 16 to the exclusion of thestent forming filament 20.

The constant force or tensioned braiding carrier 14 is useful forbraiding discrete lengths of stent forming filaments 20. With the use ofthe constant force or tensioned braiding carriers 14, all orsubstantially all of the stent forming filaments 20 are disposeddirectly within the braiding zone 32. Thus, constant tension orsubstantially constant tension on the stent forming filaments 20 iscontrolled and maintained directly within the braiding zone 32. Braidingtechniques of the prior art do not have such direct control of filamenttension within the braiding zone, leading to possible greater variationof braiding angles and stent cell sizes.

FIG. 23 is a schematic of one embodiment of the clip 18 described abovein conjunction with FIG. 1. The clip 18 is depicted as a quick releaseclip, but any clip or securing mechanism may suitably be used to securethe stent forming filament 20 to the retractable carrier filament 16.The retractable carrier filament 16 may be securably disposed toreleasably secure to the clip 18. The stent forming filament 20 isdesirably releasably secured to the clip 18. A spring 100 may be usedbetween a knob 102 and a body 104 of the clip 18. Moving the knob 102toward the clip body 104, which is against the force of the spring 100,releases the stent forming element 20 from the clip 18 by movingfilament engaging portions (not shown) within the body 104 of the clip18.

FIG. 24 schematically depicts an alternate embodiment of a constantforce bobbin carrier 110 which may be used in accordance with thepresent invention. The constant force bobbin carrier 110 includes abobbin 114 upon which the stent forming filament 20 is wound. Theconstant force bobbin carrier 110 includes a latch spring 116 whichprovides constant tension to the stent forming filament 20. The latchspring 116 typically includes an eyelet (not shown) or a small wheel toguide the stent forming filament 20. The latch spring 116 is typicallymoveable away from the bobbin 114, as indicated by the vector, toprovide tension to the stent forming filament 20. The stent formingfilament 20 then travels about a first wheel 118 and a second wheel 120.The stent forming wire 20 exits the constant force bobbin carrier 110toward the braiding zone 32 for braiding the stent 24 in accordance withthe present invention. Typically, the stent forming filament 20 ispartially unwound from one bobbin 114 and then the unwound portion isrewound onto another bobbin 114 of another the constant force bobbincarrier 110 (not shown). After the constant force bobbin carriers 110are secured to the notch gears 12, the middle portion of the stentforming filament 20 may be then engaged to the securement projections 48of the braiding mandrel 22 to braid the stent in accordance with thepresent invention. This alternative embodiment may be, however, moretime consuming as the stent filaments must be rewound onto bobbins 114.

Use of the constant force bobbin carriers 110 in conjunction with thebraiding mandrels 22, 22′ having distal securement projections 48 andbraiding channels 58 provide for suitable tension control to braid thestents of the present invention. The constant force braiding carriers110, however, may require greater lengths of filaments 20 as compared tothe use of the tensioned braiding carriers 14. As such, greater portionsof the filaments 20 may be outside the braiding zone 32 with the use ofthe bobbin carriers 110, which may lead to less direct control of thetension on the filaments 20 within the braiding zone 32.

In yet an alternate embodiment, a combination of constant force carriers14 and constant force bobbin carriers 110 may be used where instead ofrewinding the stent filament 20 onto another bobbin 114 the stentfilament end exiting the bobbin 114 may be releasably secured to aconstant force carrier 14 via the clip 18.

Desirably, the constant force carriers 14 and the constant force bobbincarrier 110, in conjunction with the other embodiments of the presentinvention, are configured and controlled to provide a controlled tensionto the filaments 16, 20 during braiding of the stent 24 over mandrel 22.Useful tension forces include substantially constant tensile forces fromabout ⅛ or 0.125 pound-force (about 0.5 Newtons) to about 10 pound-force(about 45 Newtons). Desirably, the tensile force is from about ¼ or 0.25pound-force (about 1 Newton) to about 10 pound-force (about 22 Newtons).Preferably, the tensile force is from about ½ or 0.5 pound-force (about2 Newtons) to about 3 pound-force (about 13 Newtons). In general, thelarger the diameter of the filament 20 the larger tensile force will beapplied. Minimum force levels are necessary to securely hold thefilaments 20 on the mandrel 22 during braiding and subsequent processingsteps. If too much force is applied, then the filaments 20 may stretchor deform on the mandrel 22, in particular if the stent is heat treatedwhile on the mandrel 22, which is referred to as necking of filaments orwires. Such necking is undesirable as it may weaken the filament or wireand possibly leading toward fracture of the filament or wire. Theseabove-described tensile forces are desirably useful for braidingmetallic filaments 20. When non-metallic, for example polymeric,filaments 20 are braided to form the stent 24, the tension force appliedmay be less than the values for metallic filaments 20. For example, atensile force from about 0.5 pound-force (about 2 Newton) to about 1pound-force (about 2 Newtons) is useful for braiding polymeric filaments20.

FIG. 25 depicts a method for braiding the stent 24 of the presentinvention. At step 200, a number of elongate stent filaments areprovided. Each of the filaments has opposed ends and an intermediateportion between the opposed ends. At step 210, a number of tensionedbraiding carriers is provided. At step 220, a braiding mandrel havingopposed proximal and distal ends is provided. The braiding mandrel mayinclude a number of circumferentially spaced-apart securementprojections at the distal end of the braiding mandrel and may optionallyinclude a plurality of grooves or channels for receiving the stentfilaments during braiding. At step 230, the intermediate portion of oneof the filaments is securably disposed to one of the securementprojections. At step 240, one of the opposed ends of the one filament issecured to one of the tensioned braiding carriers without spooling theone filament to the one tensioned braiding carrier. At step 250, theother opposed end of the one filament is secured to a different secondtensioned carrier without spooling the one filament to the secondtensioned carrier. At step 260, steps 230-250 are repeated until all ofthe intermediate portions of the filaments are securably disposed todifferent ones of the securement projections and until each end of thenumber of filaments are secured to a different one of the tensionedcarriers. At step 270, the tensioned carriers are moved in a generallycircular and serpentine motion. At step 280, the mandrel islongitudinally advanced relative to a direction substantiallyperpendicular to the motion of the tensioned carriers to braid thefilaments to form a braided stent.

The method of this embodiment may further include the step of applying aconstant tension from the tensioned braiding carriers to the filaments,wherein the constant tension force is form about 0.25 pound-force (1.1Newtons) to about 5 pound-force (22.2 Newtons). Further, the number ofsecurement projections may be about one-half the number of filaments,but any suitable number of securement projections may be used. Thenumber of tensioned carriers may be about twice the number of filaments,but any suitable number of tensioned carriers may be used. Desirably,the number of filaments may be from about 6 to about 40 or more. Suchnumbers of securement projections and tensioned carriers arenon-limited, and any suitable relative numbers of securement projectionsand tensioned carriers may be used. For example, the number and type offilaments 20 may be increased and/or decreased during braiding stent,including braiding different sections of stents with different types ofmaterial and/or different number of filaments.

The mandrel may include a plurality of grooves or channels and furtherwhere the filaments are disposed into the grooves during the braiding ofsteps 270 through 280. The filaments may be tangentially disposed withinthe grooves during the braiding steps 270 through 280. Desirably, thesteps 270 through 280 are continued until the filaments are braided to aportion of the mandrel near the proximal end of the mandrel. Thebraiding method may further include the step of securing the filamentsto the portion of the mandrel while maintaining the filaments under atension force from about 0.25 pound-force (1.1 Newtons) to about 5pound-force (22.2 Newtons). Further, the stent may be heat treated.Desirably, the heat treating of the stent filaments may be performedwhile the filaments are disposed on the mandrel and also while thefilaments are under the tension force.

The securement projections at the distal end of the braiding mandrel maybe selected from hooks, pins, tabs, screws and combinations thereof. Thesecurement projections may be removable from the mandrel. The distal endof the braiding material may further include a collar having thesecurement projections disposed thereto.

Further, the mandrel may include a first portion having a firstdiameter, and a second portion having a second diameter, where the firstdiameter is different from the second diameter. The mandrel may includea plurality of portions having different diameters. Moreover, themandrel may include interchangeable portions which may be connectablealong the length of the mandrel or even along the circumference of themandrel, or combinations thereof. Grooves may be disposed throughout thefirst and second portions. Further, a constant tension force may beapplied from the constant force braiding carriers to the filaments sothat a braiding angle between intersecting braided filaments issubstantially equal in the first and second portions. The mandrel mayfurther include a transition portion between the first and secondportions. Desirably, the braiding angle is substantially equal in thefirst portion, the transition portion and the second portion. Thepresent invention, however, is not so limited, and the braiding anglesmay be controlled to any custom values, including controlled variationof the braiding angle over straight stent section and non-straight stentsections, such as flared sections, flanged sections, curved sections andthe like.

The filaments may be selected from metallic filaments, polymericfilaments, and combinations thereof. The filaments may be single strandor multi-strand filaments. The strands of the multi-strand filaments maybe the same or different, such as but not limited to differentmaterials, different geometries, different mechanical properties,different physical properties, different chemical properties, and thelike. Desirably, the filaments are metallic filaments, including nitinolfilaments or nitinol-containing filaments.

FIG. 26 depicts another embodiment of a method for braiding the stent 24of the present invention. At step 300, a number of elongate filamentsare provided with each of the filaments having opposed ends and anintermediate portion between the opposed ends. At step 310, a number ofbraiding carriers are provided. At step 320, a braiding mandrel havingopposed proximal and distal ends is provided. The braiding mandrel mayinclude a number of circumferentially spaced-apart securementprojections at the distal end and may optionally further include aplurality of grooves. At step 330, the intermediate portion of one ofthe filaments is securably disposed to one of the securement projectionsat the distal end of the mandrel. At step 340, one of the opposed endsof the one filament is secured to one of the braiding carriers. At step350, the other opposed end of the one filament is secured to a differentsecond braiding carrier. At step 360, steps 330 through 350 are repeateduntil all of the intermediate portions of the filaments are securablydisposed to different ones of the securement projections and until eachend of the number of filaments are secured to a different one of thebraiding carriers. At step 370, the braiding carriers are moved in agenerally circular and serpentine motion. At step 380, the mandrel islongitudinally advanced relative to the braiding machine in a directionsubstantially perpendicular to the motion of the braiding carriers tobraid the filaments to form a braided stent; and optionally a constanttension force, for example from about 0.25 pound-force (1.1 Newtons) toabout 5 pound-force (22.2 Newtons), is applied from the braidingbarriers to the filaments during the braiding of the filaments.

The braiding carriers of this embodiment may be constant force carriers.The ends of the filaments may be securably disposed to the constantforce carriers without spooling the filaments to the constant forcecarriers. Alternatively or in addition to, some or all of the braidingcarriers may include a bobbin where a portion of the filament is spooledabout the bobbin.

While the invention has been described through the use of a braidingmachine, certain aspects of the present invention may also be usefulwith hand braiding or hand weaving method to form a stent. In such acase the braiding mandrel may further include additional tabs, pins orthe like along its longitudinal length about which a tension of thebraiding filaments may be obtained.

The stent 24 of the present invention may include a therapeutic agent ina coating. The therapeutic agent in a coating of the stent 24 of thepresent invention may be any suitable biologically acceptable agent suchas a non-genetic therapeutic agent, a biomolecule, a small molecule, orcells.

Exemplary non-genetic therapeutic agents include anti-thrombogenicagents such as heparin, heparin derivatives, prostaglandin (includingmicellar prostaglandin E1), urokinase, and PPack (dextrophenylalanineproline arginine chloromethyl ketone); anti-proliferative agents such asenoxaparin, angiopeptin, sirolimus (rapamycin), tacrolimus, everolimus,zotarolimus, biolimus, monoclonal antibodies capable of blocking smoothmuscle cell proliferation, hirudin, and acetylsalicylic acid;anti-inflammatory agents such as dexamethasone, rosiglitazone,prednisolone, corticosterone, budesonide, estrogen, estradiol,sulfasalazine, acetylsalicylic acid, mycophenolic acid, and mesalamine;anti-neoplastic/anti-proliferative/anti-mitotic agents such aspaclitaxel, epothilone, cladribine, 5-fluorouracil, methotrexate,doxorubicin, daunorubicin, cyclosporine, cisplatin, vinblastine,vincristine, epothilones, endostatin, trapidil, halofuginone, andangiostatin; anti-cancer agents such as antisense inhibitors ofc-myc-oncogene; anti-microbial agents such as triclosan, cephalosporins,aminoglycosides, nitrofurantoin, silver ions, compounds, or salts;biofilm synthesis inhibitors such as non-steroidal anti-inflammatoryagents and chelating agents such as ethylenediaminetetraacetic acid,O,O′-bis(2-aminoethyl)ethyleneglycol-N,N,N′,N′-tetraacetic acid andmixtures thereof; antibiotics such as gentamicin, rifampin, minocycline,and ciprofloxacin; antibodies including chimeric antibodies and antibodyfragments; anesthetic agents such as lidocaine, bupivacaine, andropivacaine; nitric oxide; nitric oxide (NO) donors such as linsidomine,molsidomine, L-arginine, NO-carbohydrate adducts, polymeric oroligomeric NO adducts; anti-coagulants such as D-Phe-Pro-Argchloromethyl ketone, an RGD peptide-containing compound, heparin,antithrombin compounds including anti-thrombin antibodies, plateletreceptor antagonists, anti-platelet receptor antibodies, enoxaparin,hirudin, warfarin sodium, dicumarol, aspirin, prostaglandin inhibitors,platelet aggregation inhibitors such as cilostazol and tick antiplateletfactors; vascular cell growth promoters such as growth factors,transcriptional activators, and translational promoters; vascular cellgrowth inhibitors such as growth factor inhibitors, growth factorreceptor antagonists, transcriptional repressors, translationalrepressors, replication inhibitors, inhibitory antibodies, antibodiesdirected against growth factors, bifunctional molecules consisting of agrowth factor and a cytotoxin, bifunctional molecules consisting of anantibody and a cytotoxin; cholesterol-lowering agents; vasodilatingagents; agents which interfere with endogenous vasoactive mechanisms;inhibitors of heat shock proteins such as geldanamycin; angiotensinconverting enzyme (ACE) inhibitors; beta-blockers; βAR kinase (βARK)inhibitors; phospholamban inhibitors; protein-bound particle drugs suchas ABRAXANE™; and any combinations and prodrugs of the above.

Exemplary biomolecules include peptides, polypeptides and proteins;oligonucleotides; nucleic acids such as double or single stranded DNA(including naked and cDNA), RNA, antisense nucleic acids such asantisense DNA and RNA, small interfering RNA (siRNA), and ribozymes;genes; carbohydrates; angiogenic factors including growth factors; cellcycle inhibitors; and anti-restenosis agents. Nucleic acids may beincorporated into delivery systems such as, for example, vectors(including viral vectors), plasmids or liposomes.

Non-limiting examples of proteins include SERCA 2 protein, monocytechemoattractant proteins (“MCP-1”) and bone morphogenic proteins(“BMPs”), such as, for example, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6(VGR-1), BMP-7 (OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13,BMP-14, BMP-15. Preferred BMPs are any of BMP-2, BMP-3, BMP-4, BMP-5,BMP-6, and BMP-7. These BMPs can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively, or in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNAs encodingthem. Non-limiting examples of genes include survival genes that protectagainst cell death, such as anti-apoptotic Bcl-2 family factors and Aktkinase; serca 2 gene; and combinations thereof. Non-limiting examples ofangiogenic factors include acidic and basic fibroblast growth factors,vascular endothelial growth factor, epidermal growth factor,transforming growth factors α and β, platelet-derived endothelial growthfactor, platelet-derived growth factor, tumor necrosis factor α,hepatocyte growth factor, and insulin-like growth factor. A non-limitingexample of a cell cycle inhibitor is a cathepsin D (CD) inhibitor.Non-limiting examples of anti-restenosis agents include p15, p16, p18,p19, p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase andcombinations thereof and other agents useful for interfering with cellproliferation.

Exemplary small molecules include hormones, nucleotides, amino acids,sugars, and lipids and compounds that have a molecular weight of lessthan 100 kD.

Exemplary cells include stem cells, progenitor cells, endothelial cells,adult cardiomyocytes, and smooth muscle cells. Cells can be of humanorigin (autologous or allogeneic) or from an animal source (xenogeneic),or genetically engineered. Non-limiting examples of cells include sidepopulation (SP) cells, lineage negative (Lin⁻) cells including Lin⁻CD34⁻, Lin⁻CD34⁺, Lin⁻c Kit⁺, mesenchymal stem cells includingmesenchymal stem cells with 5-aza, cord blood cells, cardiac or othertissue derived stem cells, whole bone marrow, bone marrow mononuclearcells, endothelial progenitor cells, skeletal myoblasts or satellitecells, muscle derived cells, G₀ cells, endothelial cells, adultcardiomyocytes, fibroblasts, smooth muscle cells, adult cardiacfibroblasts+5-aza, genetically modified cells, tissue engineered grafts,MyoD scar fibroblasts, pacing cells, embryonic stem cell clones,embryonic stem cells, fetal or neonatal cells, immunologically maskedcells, and teratoma derived cells.

Any of the therapeutic agents may be combined to the extent suchcombination is biologically compatible.

Any of the above mentioned therapeutic agents may be incorporated into apolymeric coating on the stent 24 or applied onto a polymeric coating onthe stent 24. The polymers of the polymeric coatings may bebiodegradable or non-biodegradable. Non-limiting examples of suitablenon-biodegradable polymers include polystyrene; polystyrene maleicanhydride; polyisobutylene copolymers such asstyrene-isobutylene-styrene block copolymers (SIBS) andstyrene-ethylene/butylene-styrene (SEBS) block copolymers;polyvinylpyrrolidone including cross-linked polyvinylpyrrolidone;polyvinyl alcohols, copolymers of vinyl monomers such as EVA; polyvinylethers; polyvinyl aromatics; polyethylene oxides; polyesters includingpolyethylene terephthalate; polyamides; polyacrylamides includingpoly(methylmethacrylate-butylacetate-methylmethacrylate) blockcopolymers; polyethers including polyether sulfone; polyalkylenesincluding polypropylene, polyethylene and high molecular weightpolyethylene; polyurethanes; polycarbonates, silicones; siloxanepolymers; cellulosic polymers such as cellulose acetate; polymerdispersions such as polyurethane dispersions (BAYHYDROL®); squaleneemulsions; and mixtures and copolymers of any of the foregoing.

Non-limiting examples of suitable biodegradable polymers includepolycarboxylic acid, polyanhydrides including maleic anhydride polymers;polyorthoesters; poly-amino acids; polyethylene oxide; polyphosphazenes;polylactic acid, polyglycolic acid and copolymers and mixtures thereofsuch as poly(L-lactic acid) (PLLA), poly(D,L-lactide), poly(lacticacid-co-glycolic acid), 50/50 (DL-lactide-co-glycolide); polydioxanone;polypropylene fumarate; polydepsipeptides; polycaprolactone andco-polymers and mixtures thereof such aspoly(D,L-lactide-co-caprolactone) and polycaprolactone co-butylacrylate; polyhydroxybutyrate valerate and blends; polycarbonates suchas tyrosine-derived polycarbonates and acrylates, polyiminocarbonates,and polydimethyltrimethylcarbonates; cyanoacrylate; calcium phosphates;polyglycosaminoglycans; macromolecules such as polysaccharides(including hyaluronic acid; cellulose, and hydroxypropyl methylcellulose; gelatin; starches; dextrans; alginates and derivativesthereof), proteins and polypeptides; and mixtures and copolymers of anyof the foregoing. The biodegradable polymer may also be a surfaceerodable polymer such as polyhydroxybutyrate and its copolymers,polycaprolactone, polyanhydrides (both crystalline and amorphous),maleic anhydride copolymers, and zinc calcium phosphate.

Such coatings used with the present invention may be formed by anymethod known to one in the art. For example, an initial polymer/solventmixture can be formed and then the therapeutic agent added to thepolymer/solvent mixture. Alternatively, the polymer, solvent, andtherapeutic agent can be added simultaneously to form the mixture. Thepolymer/solvent/therapeutic agent mixture may be a dispersion,suspension or a solution. The therapeutic agent may also be mixed withthe polymer in the absence of a solvent. The therapeutic agent may bedissolved in the polymer/solvent mixture or in the polymer to be in atrue solution with the mixture or polymer, dispersed into fine ormicronized particles in the mixture or polymer, suspended in the mixtureor polymer based on its solubility profile, or combined withmicelle-forming compounds such as surfactants or adsorbed onto smallcarrier particles to create a suspension in the mixture or polymer. Thecoating may comprise multiple polymers and/or multiple therapeuticagents.

The coating can be applied to the medical device by any known method inthe art including dipping, spraying, rolling, brushing, electrostaticplating or spinning, vapor deposition, air spraying including atomizedspray coating, and spray coating using an ultrasonic nozzle.

The coating is typically from about 1 to about 50 microns thick. It isalso within the scope of the present invention to apply multiple layersof polymer coatings onto the medical device. Such multiple layers maycontain the same or different therapeutic agents and/or the same ordifferent polymers. Methods of choosing the type, thickness and otherproperties of the polymer and/or therapeutic agent to create differentrelease kinetics are well known to one in the art.

The stent 24 may also contain a radio-opacifying agent within itsstructure to facilitate viewing the medical device during insertion andat any point while the device is implanted. Non-limiting examples ofradio-opacifying agents are bismuth subcarbonate, bismuth oxychloride,bismuth trioxide, barium sulfate, tungsten, and mixtures thereof.

The stent 24 are implanted or otherwise used in body structures,cavities, or lumens such as the vasculature, gastrointestinal tract,abdomen, peritoneum, airways, esophagus, trachea, colon, rectum, biliarytract, urinary tract, prostate, brain, spine, lung, liver, heart,skeletal muscle, kidney, bladder, intestines, stomach, pancreas, ovary,uterus, cartilage, eye, bone, joints, and the like. Further, the stent24 may contain any of the above described polymer coatings with orwithout any of the above described therapeutic agents. Moreover, onlyportions, such as but not limited to portions of the stent 24 disposedbetween stent ends 34, 38 or even just portions of one or both stentends 24, 38, may contain any of the above described polymer coatingswith or without any of the above described therapeutic agents.

The embodiments or aspects of the invention, including the embodimentspresented in the claims, may be combined in any fashion and combinationand be within the scope of the present invention. As a nonlimitingexample, the following embodiments or aspects of the invention may becombined in any fashion and combination and be within the scope of thepresent invention, as follows:

-   Embodiment 1: A method of braiding a stent comprising: (a) providing    a number of elongate filaments, each of the filaments having opposed    ends and an intermediate portion between the opposed ends; (b)    providing a number of tensioned braiding carriers; (c) providing a    braiding mandrel having opposed proximal and distal ends, the    braiding mandrel comprising a number of circumferentially    spaced-apart securement projections at the distal end of the    braiding mandrel; (d) securably disposing the intermediate portion    of one of the filaments to one of the securement projections; (e)    securing one of the opposed ends of the one filament to one of the    tensioned braiding carriers; (f) securing the other opposed end of    the one filament to a different second tensioned braiding    carrier; (g) repeating steps (d) through (f) until all of the    intermediate portions of the filaments are securably disposed to    different ones of the securement projections and until each end of    the number of filaments are secured to a different one of the    tensioned braiding carriers; (h) moving the tensioned braiding    carriers around the mandrel; and (i) longitudinally advancing the    mandrel in a direction substantially perpendicular to the motion of    the tensioned braiding carriers to braid the filaments to form a    braided stent.-   Embodiment 2: The method of embodiment 1, wherein step (h) includes    moving the tensioned braiding carriers in a generally circular and    serpentine motion about a circumferential plane of the mandrel.-   Embodiment 3: The method of embodiment 1, wherein the tensioned    braiding carriers each comprise a retractable carrier filament and    further wherein step (e) includes securing the one opposed end of    the one filament to the retractable carrier filament of the one    tensioned braiding carrier and step (f) includes securing the other    opposed end of the one filament to the retractable carrier filament    of the second tensioned braiding carrier.-   Embodiment 4: The method of embodiment 2, wherein the tensioned    braiding carriers each comprise a wheel and wherein the retractable    carrier filament of the tensioned braiding carrier is coiled about    the wheel.-   Embodiment 5: The method of embodiment 1, further comprising:    applying a constant tension from the tensioned braiding carriers to    the filaments, wherein the constant tension force is form about 0.25    pound-force to about 5 pound-force.-   Embodiment 6: The method of embodiment 1, wherein the number of    securement projections is about one-half the number of filaments.-   Embodiment 7: The method of embodiment 1, wherein the number of    tensioned braiding carriers is about twice the number of filaments.-   Embodiment 8: The method of embodiment 1, wherein the number of    filaments is from about 6 or more.-   Embodiment 9: The method of embodiment 1, wherein the mandrel    comprises a plurality of grooves and further wherein the filaments    are disposed into the grooves during the braiding of steps (h)    through (i).-   Embodiment 10: The method of embodiment 9, wherein the filaments are    tangentially disposed on the mandrel within the grooves during the    braiding steps (h) through (i).-   Embodiment 11: The method of embodiment 1, wherein the securement    projections at the distal end of the braiding mandrel are selected    from the group consisting of hooks, pins, tabs, screws and    combinations thereof.-   Embodiment 12: The method of embodiment 1, wherein the securement    projections the distal end of the braiding mandrel are removable    from the mandrel.-   Embodiment 13: The method of embodiment 1, wherein the distal end of    the braiding material further comprises a collar having the    securement projections disposed thereto, and further wherein the    securement projections are selected from the group consisting of    hooks, pins, tabs, screws and combinations thereof.-   Embodiment 14: The method of embodiment 9, wherein steps (h)    through (i) are continued until the filaments are braided to a    portion of the mandrel near the proximal end of the mandrel, and    further comprising the step of securing the filaments to the portion    of the mandrel while maintaining the filaments under a tension force    from about 0.25 pound-force to about 5 pound-force.-   Embodiment 15: The method of embodiment 14, further comprising heat    treating the filaments while the filaments are disposed on the    mandrel.-   Embodiment 16: The method of embodiment 9, wherein the mandrel    comprises a first portion having a first diameter, and a second    portion having a second diameter, wherein the first diameter is    different from the second diameter, and wherein the grooves are    disposed throughout said first and second portion, and further    comprising the step of applying a tension force from the constant    force braiding carriers to the filaments so that a braiding angle    between intersecting braided filaments is substantially equal in the    first and second portions.-   Embodiment 17: The method of embodiment 16, wherein the mandrel    further comprises a transition portion between the first and second    portions and further wherein the braiding angle is substantially    equal in the first portion, the transition portion and the second    portion.-   Embodiment 18: The method of embodiment 1, wherein the filaments are    selected from the group of metallic filaments, polymeric filaments,    and combinations thereof.-   Embodiment 19: The method of embodiment 1, wherein the filaments are    metallic filaments comprise nitinol.-   Embodiment 20: A method for braiding a stent comprising: (a)    providing a number of elongate filaments, each of the filaments    having opposed ends and an intermediate portion between the opposed    ends; (b) providing a number of braiding carriers; (c) providing a    braiding mandrel having opposed proximal and distal ends, the    braiding mandrel comprising a number of circumferentially    spaced-apart securement projections at the distal end, the mandrel    further comprising a plurality of grooves; (d) securably disposing    the intermediate portion of one of the filaments to one of the    securement projections at the distal end of the mandrel; (e)    securing one of the opposed ends of the one filament to one of the    braiding carriers; (f) securing the other opposed end of the one    filament to a different second braiding carrier; (g) repeating    steps (d) through (f) until all of the intermediate portions of the    filaments are securably disposed to different ones of the securement    projections and until each end of the number of filaments are    secured to a different one of the braiding carriers; (h) moving the    braiding carriers around the mandrel; (i) longitudinally advancing    the mandrel relative to a direction substantially perpendicular to    the motion of the braiding carriers to braid the filaments to form a    braided stent; and (j) applying a constant tension force from the    braiding barriers to the filaments during the braiding steps (h)    through (i).-   Embodiment 21: The method of embodiment 20, wherein step (h)    includes moving the braiding carriers in a generally circular and    serpentine motion about a circumferential plane of the mandrel.-   Embodiment 22: The method of embodiment 20, wherein the braiding    carriers are constant force carriers and further wherein the ends of    the filaments are securably disposed to the constant force carriers    without spooling the filaments to the constant force carriers.-   Embodiment 23: The method of embodiment 20, wherein the braiding    carriers comprise a bobbin and wherein a portion of the filament is    spooled about the bobbin.-   Embodiment 24: The method of embodiment 20, wherein the constant    tension force is from about 0.25 pound-force to about 5 pound-force.-   Embodiment 25: A method for braiding a stent comprising: (a)    providing a number of elongate filaments, each of the filaments    having opposed ends and an intermediate portion between the opposed    ends; (b) providing a number of tensioned braiding carriers; (c)    providing a braiding mandrel having opposed proximal and distal    ends, the braiding mandrel comprising a number of circumferentially    spaced-apart securement projections at the distal end, the braiding    mandrel further comprising a plurality of grooves; (d) securably    disposing the intermediate portion of one of the filaments to one of    the securement projections at the distal end of the braiding    mandrel; (e) securing one of the opposed ends of the one filament to    one of the tensioned braiding carriers without spooling the one    filament to the one tensioned braiding carrier; (f) securing the    other opposed end of the one filament to a different second    tensioned carrier without spooling the one filament to the second    tensioned carrier; (g) repeating steps (d) through (f) until all of    the intermediate portions of the filaments are securably disposed to    different ones of the securement projections and until each end of    the number of filaments are secured to a different one of the    tensioned carriers; (h) moving the tensioned carriers around the    mandrel; and (i) longitudinally advancing the mandrel relative to a    direction substantially perpendicular to the motion of the tensioned    carriers to braid the filaments by tangentially disposing the    filaments into the grooves to braid the filaments to form a braided    stent.-   Embodiment 26: The method of embodiment 25, wherein step (h)    includes moving the braiding carriers in a generally circular and    serpentine motion about a circumferential plane of the mandrel.-   Embodiment 27: The method of embodiment 25, further comprising    applying a constant tension force is from about 0.25 pound-force to    about 5 pound-force.-   Embodiment 28: A braided stent comprising: a plurality of elongate    filaments inter-braided to form a tubular well structure, the    filaments being inter-braided at a braiding angle formed at crossing    filament locations; the tubular wall structure comprising a first    portion having a first diameter, a second portion having a second    diameter which is different from the second diameter and a    transition portion disposed between the first portion and the second    portion; wherein the braiding angles in the first portion are    substantially equal, wherein the braiding angles in the second    portion are substantially equal, and wherein the braiding angles in    the transition portion are substantially equal.-   Embodiment 29: The braided stent of embodiment 28, wherein the    braiding angles in the first portion, wherein the braiding angles in    the second portion and wherein the braiding angles in the transition    portion are substantially equal.-   Embodiment 30: The braided stent of embodiment 29, wherein the    braiding angles in the first portion, the second portion and the    transition portion are all within 5 degrees of one and the other.-   Embodiment 31: The braided stent of embodiment 29, wherein the    braiding angles in the first portion, the second portion and the    transition portion are all within 1 degree of one and the other.-   Embodiment 32: The braided stent of embodiment 29, wherein the    braiding angle is an obtuse angle between longitudinally extending    inter-braided filaments.-   Embodiment 33: The braided stent of embodiment 28, wherein at least    one of the braiding angles in the first portion, in the second    portion or in the transition portion are different from the braiding    angles from the other portions.-   Embodiment 34: The braided stent of embodiment 28, wherein the    filaments are selected from the group consisting of metallic    filaments, polymeric filaments and combinations thereof.-   Embodiment 35: The braided stent of embodiment 28, wherein the    filaments are metallic filaments comprising nitinol.-   Embodiment 36: A braiding mandrel for braiding a tubular stent    comprising: an elongate tubular member having opposed proximal and    distal ends; securement projections circumferentially disposed at    spaced-apart locations at the distal end for engaging a filament    from a braiding machine; a plurality of angularly disposed grooves    along the longitudinal length of the member.-   Embodiment 37: The braiding mandrel of embodiment 36, wherein the    angularly disposed grooves extend at an angle from about 5.degree.    to about 85.degree. from a longitudinal axis of the member.-   Embodiment 38: The braiding mandrel of embodiment 36, further    comprising: a plurality of spaced-apart projections wherein spaces    between the projections define the plurality of angularly disposed    grooves in the elongate member.-   Embodiment 39: The braiding mandrel of embodiment 36, wherein the    securement projections are selected from the group consisting of    hooks, pins, tabs, screws and combinations thereof.-   Embodiment 40: The braiding mandrel of embodiment 36 further    comprising a collar disposed at the distal end of the tubular    member, wherein the securement projections are disposed on the    collar.-   Embodiment 41: The braiding mandrel of embodiment 36, wherein the    tubular member is a metallic member.-   Embodiment 42: The braiding mandrel of embodiment 36, wherein the    tubular member has a substantially constant diameter.-   Embodiment 43: The braiding mandrel of embodiment 36, wherein the    tubular member as a varied diameter.-   Embodiment 44: The method of embodiment 1, wherein step (e) is    performed without spooling the one filament to the one tensioned    braiding carrier and step (f) is performed without spooling the one    filament to the second tensioned braiding carrier.

While various embodiments of the present invention are specificallyillustrated and/or described herein, it will be appreciated thatmodifications and variations of the present invention may be effected bythose skilled in the art without departing from the spirit and intendedscope of the invention. Further, any of the embodiments or aspects ofthe invention as described in the claims or in the specification may beused with one and another without limitation.

What is claimed is:
 1. A method of making a braided stent comprising:securing a plurality of filaments to a first end of a mandrel, the firstend of the mandrel having a larger diameter than a body of the mandrel;and braiding the plurality of filaments along the first end and the bodyof the mandrel to form a stent with a flared region at a first end, theflared region having a larger diameter than a body of the stent, whereina braid angle in the flared region of the stent is substantially thesame as a braid angle in the body of the stent.
 2. The method of claim1, wherein the braid angle is 110 degrees+/−3 degrees in both the flaredregion and body of the stent.
 3. The method of claim 1, wherein braidingincludes forming the stent with closed loops at the first end of thestent and closed loops at a second end of the stent.
 4. The method ofclaim 1, wherein securing the plurality of filaments to the mandrelincludes looping an intermediate portion of each filament around one ofa plurality of securement projections on the first end of the mandrel,wherein braiding the plurality of filaments includes braiding opposingends of each filament, thereby forming the stent with closed loops atthe first end.
 5. The method of claim 4, wherein a second end of thestent is formed by bending the plurality of filaments into closed loops.6. The method of claim 4, wherein each securement projection islongitudinally and circumferentially staggered from a circumferentiallyadjacent securement projection.
 7. The method of claim 4, wherein eachsecurement projection has a single filament looped therearound.
 8. Themethod of claim 1, wherein the mandrel defines first parallel helicalpathways and second parallel helical pathways that intersect the firstparallel helical pathways, wherein during the step of braiding theplurality of filaments, one filament is positioned in each helicalpathway.
 9. The method of claim 8, wherein the mandrel has a pluralityof raised projections that define the first parallel helical pathwaysand the second parallel helical pathways, wherein during the step ofbraiding the plurality of filaments, the plurality of raised projectionsprovide for a substantially constant braiding angle for the plurality offilaments along an entirety of the stent.
 10. The method of claim 9,wherein at least one of the plurality of raised projections has apyramid shape.
 11. The method of claim 9, wherein securing the pluralityof filaments to the mandrel includes looping the plurality of filamentsaround a plurality of securement projections on the first end of themandrel, wherein the plurality of raised projections have a differentshape than a shape of the plurality of securement projections.
 12. Themethod of claim 9, wherein the mandrel includes a transition regionbetween the first end and the body of the mandrel, the transition regionbeing sloped and including some of the plurality of raised projections.13. The method of claim 1, wherein the mandrel further comprises raisedprojections aligned in a plurality bands, the plurality of bandsincluding circumferential bands and longitudinal bands, wherein theraised projections in each circumferential band are circumferentiallyoffset from the raised projections of at least one other circumferentialband, and the raised projections in each longitudinal band arelongitudinally offset from the raised projections of at least one otherlongitudinal band.
 14. A method of making a stent comprising: securingan intermediate portion of a plurality of filaments to a first end of amandrel, the mandrel having a second end and a body extending betweenthe first and second ends, the first end having a larger diameter thanthe body; braiding opposing ends of each of the plurality of filamentswith a substantially constant braid angle along an entirety of themandrel, thereby forming a stent having a flared first end region with adiameter larger than a body of the stent and a substantially constantbraid angle along an entire length of the stent.
 15. The method of claim14, wherein the braid angle is 110 degrees+/−3 degrees in both theflared first end region and body of the stent.
 16. The method of claim14, wherein braiding includes forming the stent with closed loops at asecond end of the stent.
 17. The method of claim 14, wherein the mandrelhas a plurality of raised projections that define first parallel helicalpathways and second parallel helical pathways that intersect the firstparallel helical pathways, wherein during the step of braiding, onefilament is positioned in each helical pathway and the plurality ofraised projections provide for the substantially constant braid anglealong the entire length of the stent.
 18. The method of claim 17,wherein securing the intermediate portion of the plurality of filamentsincludes looping the intermediate portion of each filament around one ofa plurality of securement projections on the first end of the mandrel,wherein each securement projection is longitudinally andcircumferentially staggered from a circumferentially adjacent securementprojection.
 19. The method of claim 18, wherein the plurality of raisedprojections all have a different shape than the plurality of securementprojections.
 20. A method of making a stent comprising: looping in anintermediate portion of each of a plurality of filaments aroundprojections at a first end of a mandrel; braiding opposing ends of eachof the plurality of filaments around a body of the mandrel to form astent having a flared first end, a body, and a second end, wherein theflared first end has a larger diameter than the body, wherein a braidangle in the flared first end is substantially the same as a braid anglein the body and the second end; and forming loops at the second end ofthe stent.